1. A family history of a genetic condition
PEDIGREE CHARTS
A family history of a genetic condition
© 2007 Paul Billiet ODWS

2. What is a pedigree chart?
Pedigree charts show a record of the family of an individual
They can be used to study the transmission of a hereditary condition
They are particularly useful when there are large families and a good family record over several generations.
© 2007 Paul Billiet ODWS

3. Studying human genetics
You cannot make humans of different types breed together
Pedigree charts offer an ethical way of studying human genetics
Today genetic engineering has new tools to offer doctors studying genetic diseases
A genetic counsellor will still use pedigree charts to help determine the distribution of a disease in an affected family
© 2007 Paul Billiet ODWS

4. Symbols used in pedigree charts
A marriage with five children, two daughters and three sons. The eldest son is affected by the condition.
Eldest child  Youngest child
Normal male
Affected male
Normal female
Affected female
Marriage
© 2007 Paul Billiet ODWS

5. Organising the pedigree chart
A pedigree chart of a family showing 20 individuals
© 2007 Paul Billiet ODWS

6. Organising the pedigree chart
Generations are identified by Roman numerals I II
III IV
© 2007 Paul Billiet ODWS

7. Organising the pedigree chart
Individuals in each generation are identified by Arabic numerals numbered from the left
Therefore the affected individuals are II3, IV2 and IV3 I II
III IV
© 2007 Paul Billiet ODWS

8. Today... Pedigree analysis
In humans, pedigree analysis is an important tool for studying inherited diseases
Pedigree analysis uses family trees and information about affected individuals to:
figure out the genetic basis of a disease or trait from its inheritance pattern
predict the risk of disease in future offspring in a family (genetic counseling)

9. Today... Pedigree analysis
How to read pedigrees
Basic patterns of inheritance
autosomal, recessive
autosomal, dominant
X-linked, recessive
X-linked, dominant (very rare)
Applying pedigree analysis - practice

10. Sample pedigree - cystic fibrosis
female
male
affected individuals

11. Autosomal recessive traits
Trait is rare in pedigree
Trait often skips generations (hidden in heterozygous carriers)
Trait affects males and females equally

12. Autosomal recessive diseases in humans
Most common ones
Cystic fibrosis
Sickle cell anemia
Phenylketonuria (PKU)
Tay-Sachs disease
For each of these, overdominance (heterozygote superiority) has been suggested as a factor in maintaining the disease alleles at high frequency in some populations

13. Autosomal dominant pedigrees
Trait is common in the pedigree
Trait is found in every generation
Affected individuals transmit the trait to ~1/2 of their children (regardless of sex)

14. ex. achondroplasia (a sketelal disorder causing dwarfism)
Autosomal dominant traits
There are few autosomal dominant human diseases (why?), but some rare traits have this inheritance pattern
ex. achondroplasia (a sketelal disorder causing dwarfism)

15. X-linked recessive pedigrees
Trait is rare in pedigree
Trait skips generations
Affected fathers DO NOT pass to their sons,
Males are more often affected than females

16. ex. Hemophilia in European royalty
X-linked recessive traits
ex. Hemophilia in European royalty

17. X-linked recessive traits
ex. Glucose-6-Phosphate Dehydrogenase deficiency
hemolytic disorder causes jaundice in infants and (often fatal) sensitivity to fava beans in adults
the most common enzyme disorder worldwide, especially in those of Mediterranean ancestry
may confer malaria resistance

18. X-linked recessive traits
ex. Glucose-6-Phosphate-Dehydrogenase deficiency

19. X-linked dominant pedigrees
Trait is common in pedigree
Affected fathers pass to ALL of their daughters
Males and females are equally likely to be affected

20. X-linked dominant diseases
X-linked dominant diseases are extremely unusual
Often, they are lethal (before birth) in males and only seen in females
ex. incontinentia pigmenti (skin lesions)
ex. X-linked rickets (bone lesions)

21. Pedigree Analysis in real life: complications
Incomplete Penetrance of autosomal dominant traits
=> not everyone with genotype expresses trait at all
Ex. Breast cancer genes BRCA-1 and BRCA-2
& many “genetic tendencies” for human diseases

22. Pedigree Analysis in real life: complications
Sex-limited expression
=> trait only found in males OR females

23. Pedigree Analysis in real life
Remember:
dominant traits may be rare in population
recessive traits may be common in population
alleles may come into the pedigree from 2 sources
mutation happens
often traits are more complex
affected by environment & other genes

24. What is the pattern of inheritance?
What are IV-2’s odds of being a carrier?

25. Sample pedigree - cystic fibrosis
What can we say about I-1 and I-2?
What can we say about II-4 and II-5?
What are the odds that III-5 is a carrier?
What can we say about gene frequency?

26. What is the inheritance pattern?
What is the genotype of III-1, III-2, and II-3?
What are the odds that IV-5 would have an affected son?

27. III-1 has 12 kids with an unaffected wife
8 sons - 1 affected
4 daughters - 2 affected
Does he have reason to be concerned about paternity?

28. Breeding the perfect Black Lab
How do we get a true-breeding line for both traits??
black individuals = fetch well
grey individuals = don’t drool